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Title: The role of adipose and skeletal muscle derived cytokines in primary human myogenesis : implications for ageing skeletal muscle
Author: O'Leary, Mary Frances
ISNI:       0000 0004 7230 541X
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2018
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Sarcopenia is the age-related loss of skeletal muscle mass and function; inflammation is thought to be one aetiological factor in its development. Adipose tissue accumulates with advancing age and adipose-derived cytokines (adipokines) contribute to inflammaging. Skeletal muscle myogenesis is one adaptaive mechanism by which skeletal muscle mass is sustained throughout the human lifespan. The effect of the adipose inflammatory milieu on such myogenesis is unknown, as is the relative importance of its constituent adipokines to myogenesis. This work demonstrates that conditioned medium generated from obese subcutaneuous adipose tissue has a detrimental effect on in vitro primary human myogenesis. Resistin is shown to be – in part – responsible for this phenomenon and is demonstrated to inhibit myogenesis by activating the classical NFκB pathway. Resistin is further shown to be a metabolic stressor of primary human myotubes, promoting increased oxygen consumption, fatty acid oxidation and lipid accumulation. It is important to identify more avenues for the development of pharmacological interventions in sarcopenia. To that end, this thesis also demonstrates for the first time that the myokine IL-15: 1) is pro-myogenic in primary human cultures; 2) can mitigate the detrimental effects of an inflammatory environment on myogenesis; and 3) supports myogenesis at autocrine concentrations.
Supervisor: Not available Sponsor: Wellcome Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RM Therapeutics. Pharmacology